Plasma apolipoproteins are isolated in the Branch for a variety of studies including structural analysis, ligands for cellular receptors and cholesterol efflux, and human and animal kinetic studies. Lipoprotein particles with defined apolipoprotein composition are isolated by affinity chromatography and FPLC. Lipoprotein particles are utilized for human and mouse kinetic studies as well as cell culture studies. LpE has been proposed to play a major role in cholesterol efflux and transport cholesterol by the process of reverse cholesterol transport to the liver for removal from the body. Detailed studies of LpE in control plasma and plasma from patients with Tangier disease and abetalipoproteinemia have revealed that LpE is heterogeneous with particles containing LpE, LpE:A-I and LpE:A-I:A-II. LpE, LpE:A-I and LpE:A-I:A-II have been purified to homogeneity using a combination of gel filtration and affinity chromatography. These LpE containing lipoprotein particles have been used in human kinetic studies to determine the metabolism and metabolic relationship between the LpE particles within plasma. Initial studies with 125I LpE and LpE:A-I in normal control subjects have indicated that LpE and LpE:A-I are catabolized at a much faster rate than LpA-I and LpA-I:A-II particles. LpE particles were tested for their ability to efflux cholesterol from cells in culture. The efflux of control and apoE def serum from FU5AH was similar at 6.8 plus/minus 0.2/h and 6.7 plus/minus 0.8/h respectively whereas the efflux with serum from an apoA-I deficient patient was decreased 75% (1.5% plus/minus 0.1/h). No change in cholesterol efflux was observed with the addition of apoE (40ug/ml) to apoE deficient serum (4.5% plus/minus 0.1/h vs 4.2 plus/minus 0.3/h). ApoE and apoE/phospholipid complexes mediated cholesterol efflux but LpE particles did not promote cholesterol efflux. ApoA-I and /or A-II on LpE particles restores the ability to efflux cholesterol. These results indicate that the total LpE particles in serum only a subset of lipid poor apoE lipoproteins may be effective in cholesterol efflux.